Abstract
Spin-freeze-drying is a promising technique to enable long-term storage of pharmaceutical unit doses of aqueous drug solutions. To investigate the sublimation of the ice during the primary phase of freeze-drying, X-ray imaging can yield crucial temporally resolved information on the local dynamics. In this paper, we describe a methodology to investigate the sublimation front during single unit-dose freeze-drying using 4D in-situ X-ray imaging. Three spin-frozen samples of different solutions were imaged using this methodology and the process characteristics were analysed and reduced to two-dimensional feature maps.
Highlights
Freeze-drying or lyophilisation is a low-temperature drying process to stabilize heat-sensitive bio-pharmaceutical materials for storage and distribution
We present a methodology for operando X-ray imaging of spin-freezing of pharmaceutical samples and analyzing the sublimation front in this process
The two solutions have a high collapse temperature (Tc ) (−9 ° C for bovine serum albumin (BSA) and −2 ° C for mannitol) [36], which minimizes the risk ofcollapse during the dynamic imaging experiments. These solutions were chosen for their different structure in solid state, being amorphous for the BSA
Summary
Freeze-drying or lyophilisation is a low-temperature drying process to stabilize heat-sensitive bio-pharmaceutical materials for storage and distribution. Since the surface area of the frozen substance is spread over the vial’s wall as a thin layer, this allows for a significantly higher sublimation rate during the drying steps as compared with the traditional technique and results in decreased variations from vial to vial. These intra-vial fluctuations of the sublimation process can be monitored on a single vial level using thermal imaging [6,7,8]. This technique, often named 4D micro-CT, has been applied already in a large number of Materials 2020, 13, 2953; doi:10.3390/ma13132953 www.mdpi.com/journal/materials
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